Background Liver stiffness measurement has been proposed as a noninvasive marker for predicting liver-related complications of cirrhosis. Purpose To evaluate the predictive value of liver stiffness measurement by using two-dimensional (2D) shear-wave elastography (SWE) for liver-related events among patients with chronic hepatitis B. Materials and Methods This retrospective study recruited consecutive patients with chronic hepatitis B who were referred for liver biopsy between May 2011 and May 2015. All patients underwent 2D SWE before biopsy, and a subset of patients underwent transient elastography. Patients were followed up for 4 years through the electronic medical records or telephone interviews. Univariable and multivariable logistic regression analyses were used to determine prognostic factors. Accuracy of prognostic parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). Results Among 430 patients (mean age, 38 years; range, 18-67 years) including 328 men and 102 women, 29 patients developed liver-related events. Multivariable analysis demonstrated that liver stiffness measured with 2D SWE, spleen longitudinal diameter at US, age, and albumin level were predictive factors of liver-related events. The AUC of the multivariable model was higher (0.89; 95% confidence interval [CI]: 0.86, 0.92) but not significantly different from that of 2D SWE (0.86; 95% CI: 0.82, 0.89; P = .23) and was significantly higher than that of the fibrosis stage (0.72; 95% CI: 0.68, 0.76; P < .001), the aspartate aminotransferase-to-platelet ratio index (0.80; 95% CI: 0.76, 0.84; P < .001), and the fibrosis-4 index (0.84; 95% CI: 0.80, 0.87; P = .02). In a subset of patients with available transient elastography (n = 188), the multivariable model, 2D SWE, and transient elastography showed comparable performance (AUC: 0.91 vs 0.86 vs 0.88, respectively). When inflammatory activity was considered, the multivariable model was highly accurate in patients with low-grade inflammation and normal levels of alanine aminotransferase (AUC: 0.97 and 0.94, respectively). Conclusion The multivariable model and two-dimensional shear-wave elastography are more accurate in predicting liver-related events than are the fibrosis stage and serum markers of liver fibrosis tests. © RSNA, 2020 Online supplemental material is available for this article.